Large population cell characterization using quantitative phase cytometer

Abstract

A major challenge in cellular analysis is the phenotypic characterization of large cell populations within a short period of time. Among various parameters for cell characterization, the cell dry mass is often used to describe cell size but is difficult to be measured directly with traditional techniques. Here, we propose an interferometric approach based on line-focused beam illumination for high-content precision dry mass measurements of adherent cells in a non-invasive fashion—we call it quantitative phase cytometry (QPC). Besides dry mass, abundant cellular morphological features such as projected area, sphericity, and phase skewness can be readily extracted from the QPC interferometric data. To validate the utility of our technique, we demonstrate characterizing a large population of ~104 HeLa cells. Our reported QPC system is envisioned as a promising quantitative tool for label-free characterization of a large cell count at single cell resolution.

Quantitative Phase Imaging for Label-Free Analysis of Cancer Cells—Focus on Digital Holographic Microscopy

“…The ability to measure cell count was validated for the first time in 2008 by Mölder et al [21], using human breast and prostate cancer cell lines, as well as a mouse fibroblast cell line. Measurement of cell growth has been well documented for both adherent and non-adherent cells [8,9,15,[25][26][27][28]47,49,56,59,61]. By segmentation of cellular outlines, morphology and motility can also be studied [7,50,51,57,80].…”

New editor on the block

“…Jin's current efforts are focused toward the development of user‐friendly analytical devices to test for tiny quantities of materials that may be early signals of disease, signs of drugs, or evidence of food or environmental toxins . To achieve this, he has established the ARC Industry Transformation Research Hub for Integrated Device for End‐user Analysis at Low‐levels (idealresearchhub.com).…”

Multi‐ATOM: Ultrahigh‐throughput single‐cell quantitative phase imaging with subcellular resolution

“…In the current QPI approaches, the subcellular resolution is commonly achieved at the expense of the imaging throughput which is limited to only a few tens to hundreds of cells within a field of view (FOV) . Despite that the throughput problem can partially be alleviated through automated sample scanning (up to ~10 4 cells) , it is further exacerbated by the inherent limitations of current camera technology, that is, severe image motion blur, degradation in image resolution and loss of detection sensitivity at high speed. This also explains the limited flow rate and thus single‐cell imaging throughput in the available QPI flow cytometers .…”